The axonal growth cone is critical to the development and maintenance of the uniquely complex and specific synaptic connections which underlie nervous system function. GAP-43 is a neuronal protein whose expression is closely correlated with growth cone activity in development and regeneration, and with synaptic plasticity. Homologous recombination will be employed to develop animals and cell lines incapable of expressing GAP-43. This technique relies on crossing over between an exogenous mutated DNA molecule and the endogenous gene to replace a normal allele with a mutated copy. In animals and cell lines with deletion of GAP-43, the importance of the protein for growth cone function will be analyzed. This information will allow creation of models and perhaps rational therapies for some disease states in which neural development, regeneration or plasticity are flawed. Examples include developmental disorders, neurite regeneration in neuropathy and perhaps in recovery from central injuries like stroke, and learning in memory disorders with impaired synaptic plasticity.